In article <42ikps$kqt at agate.berkeley.edu>,
frauwirt at notmendel.Berkeley.EDU (Ken Frauwirth (BioKen)) wrote:
> In article <v01510100ac7230de035f@[128.173.187.15]>,
> Klaus D. Elgert <kdelgert at vt.edu> wrote:
> >Immunology netters:
> >
> >Along the recent lines of posting questions asked, in this case, by a
> >graduate student during an undergraduate immunology lecture on antigens. I
> >told her to see me later in the week, so how about some help before she
> >gets here. The jest of her two questions was something like this (I
> >think). We have a B cell specific for antigen X. It captures antigen X by
> >its antibody receptors. These antibody receptors are directed against a
> >specific epitope. Question 1: Once the B cell internalizes antigen X, how
> >does it display (or know to display) the same epitope (peptide) by its
> >class II molecules to the appropriate Th cell TCR? Question 2: If it is
> >the same epitope, how does this Th cell become primed to the same peptide,
> >through macrophage peptide-class II complex presentation, so that it can
> >help the appropriate anti-X B cell? (When T cells do not recognize the
> >same epitopes that B cells do.) This B cell then undergoes differentiation
> >into a plasma cell, secreting antibody that reacts to the capture epitope.
> >
>> The answer to this is that the antibody epitope and the T cell epitope need
> not be the same (in fact, they are generally distinct). The antibody
> epitope is defined by the random recombination of the antibody genes and
> can be just about anywhere on the antigen. The T cell epitopes are limited
> by the antigen processing machinery, which is why B cells and macrophages can
> display the same peptide/MHC complexes.
>> This separation of the T and B cell epitopes is best exemplified by the
> "carrier effect". In order to get an good immune response to a hapten, it
> is usually conjugated to a "carrier" protein (such as KLH or BSA) which
> contains many potential T cell epitopes (a hapten cannot by itself be a T cell
> epitope). The B cell internalizes the complex using a hapten-specific surface
> Ig molecule, and presents carrier-derived epitopes on MHC Class II to T cells.
> In the meantime, the T cells can be primed by macrophages or dendritic cells
> which internalize the carrier/hapten nonspecifically, and the B cells can
> receive help to differentiate into a hapten-specific plasma cell, undergo
> class-switching, etc.
>Also, it is important to consider that the TCR does not only bind to the
peptide presented by MHC. In fact it binds to the 3-D product made up by
MHC+peptide and the majority of what it binds is the MHC. Most of the
amino acids of the peptide will be hidden in the peptide binding groove of
the MHC and only a few amino acids will be exposed to the TCR. Note also
that the 3-D structure of the MHC alters depending on which peptide it
binds.
Mårten Schneider, Dept. of medical immunology and microbiology, Uppsala, Sweden.
(Marten.Schneider at immun.uu.se)